Nanotechnology has considerable promise for the detection, staging and treatment of cancer. Here, we outline one such promising application: the use of nanostructures with surface-bound ligands for the targeted delivery and ablation of colorectal cancer (CRC), the third most common malignancy and the second most common cause of cancer-related mortality in the US. Normal colonic epithelial cells as well as primary CRC and metastatic tumors all express a unique surface-bound guanylyl cyclase C (GCC), which binds the diarrheagenic bacterial heat-stable peptide enterotoxin ST. This makes GCC a potential target for metastatic tumor ablation using ST-bound nanoparticles in combination with thermal ablation with near-infrared or radiofrequency energy absorption. Furthermore, the incorporation of iron or iron oxide into such structures would provide advantages for magnetic resonance imaging (MRI). Although the scenarios outlined in this article are hypothetical, they might stimulate ideas about how other cancers could be attacked using nanotechnology.